Dataset Information

Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals.

ABSTRACT: Background: Saturated fat (SFA) has consistently been shown to increase liver fat, but the response appears variable at the individual level. Phenotypic and genotypic characteristics have been demonstrated to modify the hypercholesterolemic effect of SFA but it is unclear which characteristics that predict liver fat accumulation in response to a hypercaloric diet high in SFA. Objective: To identify predictors of liver fat accumulation in response to an increased intake of SFA. Design: We pooled our two previously conducted double-blind randomized trials (LIPOGAIN and LIPOGAIN-2, clinicaltrials.gov NCT01427140 and NCT02211612) and used data from the n = 49 metabolically healthy men (n = 32) and women (n = 17) randomized to a hypercaloric diet through addition of SFA-rich muffins for 7-8 weeks. Associations between clinical and metabolic variables at baseline and changes in liver fat during the intervention were analyzed using Spearman rank correlation. Linear regression was used to generate a prediction model. Results: Liver fat increased by 33% (IQR 5.4-82.7%; P < 0.0001) in response to excess energy intake and this was not associated (r = 0.17, P = 0.23) with the increase in body weight (1.9 kg; IQR 1.1-2.9 kg). Liver fat accumulation was similar (P = 0.28) in carriers (33%, IQR 14-79%) and non-carriers (33%, IQR -11 to +87%) of the PNPLA3-I148M variant. Baseline visceral and liver fat content, as well as levels of the liver enzyme ?-glutamyl transferase (GT), were the strongest positive predictors of liver fat accumulation-in contrast, adiponectin and the fatty acid 17:0 in adipose tissue were the only negative predictors in univariate analyses. A regression model based on eight clinical and metabolic variables could explain 81% of the variation in liver fat accumulation. Conclusion: Our results suggest there exists a highly inter-individual variation in the accumulation of liver fat in metabolically healthy men and women, in response to an increased energy intake from SFA and carbohydrates that occurs over circa 2 months. This marked variability in liver fat accumulation could largely be predicted by a set of clinical (e.g., GT and BMI) and metabolic (e.g., fatty acids, HOMA-IR, and adiponectin) variables assessed at baseline.

SUBMITTER: Rosqvist F

PROVIDER: S-EPMC7744344 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals.

Rosqvist Fredrik F Orho-Melander Marju M Kullberg Joel J Iggman David D Johansson Hans-Erik HE Cedernaes Jonathan J Ahlström Håkan H Risérus Ulf U

Frontiers in nutrition 20201203

Background: Saturated fat (SFA) has consistently been shown to increase liver fat, but the response appears variable at the individual level. Phenotypic and genotypic characteristics have been demonstrated to modify the hypercholesterolemic effect of SFA but it is unclear which characteristics that predict liver fat accumulation in response to a hypercaloric diet high in SFA. Objective: To identify predictors of liver fat accumulation in response to an increased intake of SFA. D ...[more]

PMID: 33344496

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Project description:ObjectiveThe aim of dietary modification, as a cornerstone of type 2 diabetes (T2DM) management, is to optimise metabolic control and overall health. This study describes food and nutrient intake in a sample of adults with T2DM, and compares this to recommendations, and to intake in age, sex, body mass index (BMI) and social-class matched adults without T2DM.DesignA cross-sectional analysis of food and nutrient intake in 124 T2DM individuals (64% male; age 57.4±5.6 years, BMI 32.5±5.8 kg m(-2)) and 124 adults (age 57.4±7.0 years, BMI 31.2±5.0 kg m(-2)) with no diabetes (ND) was undertaken using a 4-day semiweighed food diary. Biochemical and anthropometric variables were also measured.ResultsWhile reported energy intake was similar in T2DM vs ND (1954 vs 2004 kcal per day, P=0.99), T2DM subjects consumed more total-fat (38.8% vs 35%, P0.001), monounsaturated-fat (13.3% vs 12.2%; P=0.004), polyunsaturated-fat (6.7% vs 5.9%; P<0.001) and protein (18.6% vs 17.5%, P0.01). Both groups exceeded saturated-fat recommendations (14.0% vs 13.8%). T2DM intakes of carbohydrate (39.5% vs 42.9%), non-milk sugar (10.4% vs 15.0%) and fibre (14.4 vs 18.9 g) were significantly lower (P<0.001). Dietary glycaemic load (GL) was also lower in T2DM (120.8 vs 129.2; P=0.02), despite a similar glycaemic index (59.7 vs 60.1; P=0.48). T2DM individuals reported consuming significantly more wholemeal/brown/wholegrain breads, eggs, oils, vegetables, meat/meat products, savoury snacks and soups/sauces and less white breads, breakfast cereals, cakes/buns, full-fat dairy, chocolate, fruit juices, oily fish and alcohol than ND controls.ConclusionAdults with T2DM made different food choices to ND adults. This resulted in a high saturated-fat diet, with a higher total-fat, monounsaturated-fat, polyunsaturated-fat and protein content and a lower GL, carbohydrate, fibre and non-milk sugar content. Dietary education should emphasise and reinforce the importance of higher fibre, fruit, vegetable and wholegrain intake and the substitution of monounsaturated for saturated-fat sources, in energy balanced conditions.

Project description:BackgroundAccumulation of saturated fatty acids (SFAs) in the liver is known to induce hepatic steatosis and inflammation causing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although SFAs have been shown to affect the epigenome in whole blood, pancreatic islets, and adipose tissue in humans, and genome-wide DNA methylation studies have linked epigenetic changes to NAFLD and NASH, studies focusing on the association of SFAs and DNA methylation in human liver are missing. We, therefore, investigated whether human liver SFA content associates with DNA methylation and tested if SFA-linked alterations in DNA methylation associate with NAFLD-related clinical phenotypes in obese individuals.ResultsWe identified DNA methylation (Infinium HumanMethylation450 BeadChip) of 3169 CpGs to be associated with liver total SFA content (q-value < 0.05) measured using proton NMR spectroscopy in participants of the Kuopio Obesity Surgery Study (n = 51; mean ± SD:49.3 ± 8.5 years old; BMI:43.7 ± 6.2 kg/m2). Of these 3169 sites, 797 overlapped with previously published NASH-associated CpGs (NASH-SFA), while 2372 CpGs were exclusively associated with SFA (Only-SFA). The corresponding annotated genes of these only-SFA CpGs were found to be enriched in pathways linked to satiety and hunger. Among the 54 genes mapping to these enriched pathways, DNA methylation of CpGs mapping to PRKCA and TSPO correlated with their own mRNA expression (HumanHT-12 Expression BeadChip). In addition, DNA methylation of another ten of these CpGs correlated with the mRNA expression of their neighboring genes (p value < 0.05). The proportion of CpGs demonstrating a correlation of DNA methylation with plasma glucose was higher in NASH-SFA and only-SFA groups, while the proportion of significant correlations with plasma insulin was higher in only-NASH and NASH-SFA groups as compared to all CpGs on the Illumina 450 K array (Illumina, San Diego, CA, USA).ConclusionsOur results suggest that one of the mechanisms how SFA could contribute to metabolic dysregulation in NAFLD is at the level of DNA methylation. We further propose that liver SFA-related DNA methylation profile may contribute more to hyperglycemia, while insulin-related methylation profile is more linked to NAFLD or NASH. Further research is needed to elucidate the molecular mechanisms behind these observations.

Project description:BackgroundThe putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.ObjectiveThe aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.DesignWe conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites.ResultsIn the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar results were observed in the GOLDN Study and the FHS. Additionally, in the FHS, cg04436964 methylation was negatively correlated with APOA2 expression in the blood of participants consuming a high-SFA diet. Furthermore, when consuming a high-SFA diet, CC carriers had lower APOA2 expression than those with the TT genotype. Lastly, metabolomic analysis identified 4 pathways as overrepresented by metabolite differences between CC and TT genotypes with high-SFA intake, including tryptophan and branched-chain amino acid (BCAA) pathways. Interestingly, these pathways were linked to rs5082-specific cg04436964 methylation differences in high-SFA consumers.ConclusionsThe epigenetic status of the APOA2 regulatory region is associated with SFA intake and APOA2 -265T>C genotype, promoting an APOA2 expression difference between APOA2 genotypes on a high-SFA diet, and modulating BCAA and tryptophan metabolic pathways. These findings identify potential mechanisms by which this highly reproducible gene-diet interaction influences obesity risk, and contribute new insights to ongoing investigations of the relation between SFA and human health. This study was registered at clinicaltrials.gov as NCT03452787.

Dataset Information

Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals.

Publications

Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals.

Similar Datasets

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